Clinical and Metabolic Characteristics of Non-Alcoholic Fatty Liver Disease Patients in Saudi Arabia: Data from the Systematic Observatory Liver Disease (SOLID) Registry.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in Saudi Arabia (SA), but descriptions of the clinical and metabolic characteristics of these patients are limited. The present study aims to fill this gap. METHODS: Demographic, clinical, and laboratory data of all NAFLD patients from 2009 to 2019 were retrieved from the Systematic Observatory Liver Disease Registry (SOLID) [n=832 (337 males; 495 females); mean (± standard deviation, SD) age was 42.6±13.6 years; mean body mass index (BMI) was 35.0±9.3kg/m2]. Non-invasive surrogate scores of fibrosis (eg AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4), and NAFLD fibrosis (NFS) scores) were calculated and analyzed. In addition, data from NAFLD patients with normal and high alanine aminotransferase (ALT) were compared using two different methods: the standard laboratory reference range which defines normal as ALT<61 IU/L, and the range proposed by a recent national study which sets upper limits of normal ALT at 33 IU/l for men and 22 IU/l for women. RESULTS: Hyperlipidemia was the most common comorbidity (41.7%), followed by type 2 diabetes mellitus (T2DM) (35.3%) and hypertension (28.4%). Prevalence of advanced fibrosis varied widely across definitions [FIB-4, N=19 (2.5%); APRI, N=21 (2.8%); NFS, N=62 (8.6%)] and exhibited sexual dimorphism with males having worse metabolic characteristics. NAFLD patients with normal ALT were more likely to be older, female, have a lower BMI, and have a higher prevalence of cirrhosis, DM, hypertension, hyperlipidemia, and renal dysfunction. CONCLUSION: Patients with NAFLD have metabolic characteristics associated with several comorbidities, including NAFLD patients with normal ALT. Mechanistic studies are needed to examine and analyze complex, interactive effects between sex, age, and other factors that may accelerate NAFLD disease progression.

Demyelinating polyneuropathy associated with chronic inactive hepatitis B infection.

This is a case report of a 42-year-old female patient with chronic inactive hepatitis B virus (HBV) infection who presented with relapsing chronic inflammatory demyelinating polyneuropathy (CIDP). Her initial attack was of acute onset (ie, acute CIDP) resembling Guillain-Barré syndrome that responded well to intravenous immunoglobulin (IVIG) therapy. The second episode was chronic and refractory to IVIG. She was managed with plasma exchange, long-term corticosteroids, immunosuppressants and HBV antiviral therapy. She showed both clinical and electromyographic improvement, with no recurrence after 2 years of follow-up.

Clinical Characteristics of Hepatitis B Virus Patients After Switching to Tenofovir Alafenamide Fumarate: A Retrospective Observational Study.

Background Hepatitis B Virus (HBV) continues to be a significant global health problem despite vaccination programs and effective antiviral drugs. Aim Assess tenofovir alafenamide fumarate (TAF) as a new treatment modality in light of the clinical characteristics of HBV patients. Settings and design A real-world observational study Methods and material We collected data of 71 HBV patients and recorded the hepatitis B virus deoxyribonucleic acid (HBV-DNA) plasma levels and biochemistry test results for the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine levels at three time points, including baseline, time of switching to TAF, and six months after switching. Results From the time of switching to TAF till six months later, HBV-DNA plasma levels significantly decreased from 838.61 IU/mL to 16.7 IU/mL (p-value of <0.05). ALT and AST levels dropped from 29.05 U/L to 27 U/L and from 21.34 U/L to 20.7 U/L (p-values 0.328 and 0.410, respectively). Although TAF did not show a statistically significant reduction in the serum levels of AST, ALT, and creatinine, it showed a detectable maintenance level. Conclusions In the evaluated cohort, all clinical characteristics of HBV were maintained six months after switching patients to TAF.

Hepatitis B care pathway in Saudi Arabia: Current situation, gaps and actions.

Hepatitis B virus (HBV) infection remains a public health problem worldwide. In this review, we aim to assess the current situation of the HBV care pathway in the Kingdom of Saudi Arabia (KSA), identify gaps/barriers therein, and recommend initiatives to be taken to improve the management of such patients. Towards this end, a literature search was conducted in PubMed and free Internet searches. Interviews with individuals and focus group discussions were held with HBV experts in KSA. Although significant improvements have been made in the past 30 years in KSA in terms of the decline in prevalence (currently estimated to be around 1.3%), the morbidity and mortality related to the disease have not shown a parallel decline. This makes HBV an important public health concern. Furthermore, poor disease awareness, low diagnosis rates, and nonadherence to therapy amplify the disease burden. There are several mandated national screening structures present; however, established protocols for those who test positive and subsequent linkage-to-care are inadequate. In the absence of a virologic cure, a concerted effort should be made to provide safe and effective lifelong treatment. This review provides recommendations to reduce the HBV disease burden in the Saudi population.

Nonalcoholic fatty liver disease burden - Saudi Arabia and United Arab Emirates, 2017-2030.

Background/Aim: Due to epidemic levels of obesity and type 2 diabetes mellitus (DM), nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) will be driving factors in liver disease burden in the coming years in Saudi Arabia and United Arab Emirates (UAE). Materials and Methods: Models were used to estimate NAFLD and NASH disease progression, primarily based on changes in adult prevalence rates of adult obesity and DM. The published estimates and expert interviews were used to build and validate the model projections. Results: In both countries, the prevalence of NAFLD increased through 2030 parallel to projected increases in the prevalence of obesity and DM. By 2030, there were an estimated 12,534,000 NAFLD cases in Saudi Arabia and 372,000 cases in UAE. Increases in NASH cases were relatively greater than the NAFLD cases due to aging of the population and disease progression. Likewise, prevalent cases of compensated cirrhosis and advanced liver disease are projected to at least double by 2030, while annual incident liver deaths increase in both countries to 4800 deaths in Saudi Arabia and 140 deaths in UAE. Conclusions: Continued high rates of adult obesity and DM, in combination with aging populations, suggest that advanced liver disease and mortality attributable to NAFLD/NASH will increase across both countries. Reducing the growth of the NAFLD population, along with potential therapeutic options, will be needed to reduce liver disease burden.

Real life efficacy of ledipasvir/sofosbuvir in hepatitis C genotype 4-infected patients with advanced liver fibrosis and decompensated cirrhosis.

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. PATIENTS & METHODS: This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). RESULTS: The mean age of the overall cohort was 59.6 ±â€¯12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). CONCLUSION: LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.

High Efficacy of ombitasvir/paritaprevir/ritonavir plus dasabuvir in hepatitis C genotypes 4 and 1-infected patients with severe chronic kidney disease.

BACKGROUND & AIMS: Limited data have shown high efficacy of co-formulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in the treatment of hepatitis C virus (HCV) genotype (GT)-4, and combined with dasabuvir (DSV) in GT1 patients, with chronic kidney disease (CKD) stages 4-5 (<30 mL/min/1.73 m2 ). We assessed real-world safety and efficacy of OBV/PTV/r ± DSV in GT1- and 4-infected patients. METHODS: In this observational cohort (n = 67), we enrolled stages 4-5 CKD treatment-naïve or Peginterferon/RBV-experienced GT4-infected patients (n = 32) treated for 12-24 weeks with OBV/PTV/r ± RBV, and plus DSV in GT1 patients (n = 35, including 3 with GT1/4 co-infection). RBV was dosed by physician discretion between 200 mg weekly and 200 mg daily. Primary endpoints were SVR12, calculated on intention-to-treat (ITT) basis, and occurrence of serious adverse events. RESULTS: The mean age of the cohort was 45.7 ± 12.7 years, 50.7% were females, 20.9% had cirrhosis, 35.8% were treatment-experienced and 97% were on haemodialysis. Three patients (F4) received 24-week treatment, 2 with GT4, and 1 with GT1a; and 19.4% were treated without RBV, including 9 GT1, and 4 GT4. Overall, 65 (97.1%) patients achieved SVR12, including 100% of those with a post-treatment follow-up (modified ITT analysis). Of the two patients without SVR12, one died from sepsis-related complications and the other from a myocardial infarction 2 weeks after completing therapy. Grades 3-4 anaemia occurred in 8.9%. CONCLUSION: A 12-week regimen of OBV/PTV/r ± DSV with or without RBV is highly effective with a favourable safety profile amongst GT4 and GT1 patients with CKD stages 4-5. SVR12 rates were high regardless of patient characteristics.

Analysis of Hepatitis B virus (HBV) mutations in patients from Western Saudi Arabia with chronic disease.

INTRODUCTION: Extensive research has provided a link between HBV variants and the clinical complications of liver diseases. This study was performed to further investigate the relationship between HBV variants in preS, S and BCP/PC regions and disease progression in chronic hepatitis B (CHB) cases in Jeddah, Saudi Arabia. METHODOLOGY: 182 CHB patients were recruited for this study. HBV DNA was amplified by PCR in the PreS, S, and BCP/PC regions. Sequences were generated from 31 and 26 treated cases in PreS and S regions respectively and from 72 cases in the BCP/PC region. RESULTS: The majority of cases (86.7%) were genotype D. Mutations at preS1-A2922C, X-A1624C and PC-G1887A were detected only in cases with either a high fibrosis score or hepatocellular carcinoma (HCC), while mutations at positions PC-C1982A, PC-G1951T, X-C1628T and X-A1630G were detected more frequently in HCC cases, without reaching statistical significance. Seven deletions were detected in the PreS-region. No deletions were detected in the CCAAT box. The accumulation of mutations per sample in the preS1-2 and S regions were associated with elevated ALT (p < 0.001, 0.001 and 0.001; respectively) and increased fibrosis (p = 0.018, 0.02 and 0.013; respectively). The accumulation of mutations per sample in the BCP/PC region is associated with high viral load. Occult hepatitis B infection (OBI) was identified in 5 samples. CONCLUSION: Our results add to the knowledge about HBV genotype-D variants. The accumulation of mutations per sample and OBI seem to play a role in the progression of HBV infection. G1896A was associated with the HBeAg negativity. The preS deletions did not play a role in liver disease progression.

Epidemiology, disease burden, and treatment strategies of chronic hepatitis C virus infections in Saudi Arabia in the new treatment paradigm shift.

BACKGROUND/AIMS: Around 101,000 individuals are estimated to be viremic for chronic hepatitis C virus (HCV) in the Kingdom of Saudi Arabia (KSA) in 2014; however, only about 20% have been diagnosed. We aim to assess baseline epidemiology, disease burden, and evaluate strategies to eliminate HCV in KSA. MATERIALS AND METHODS: The infected population and disease progression were modeled using age- and gender-defined cohorts to track HCV incidence, prevalence, hepatic complications, and mortality. Baseline assumptions and transition probabilities were extracted from the literature. The impacts of two scenarios on HCV-related disease burden were considered through increases in treatment efficacy alone or treatment and diagnosis. RESULTS: In 2030, it is estimated by the base scenario that viremic prevalence will increase to 103,000 cases, hepatocellular carcinoma (HCC) to 470, decompensated and compensated cirrhosis cases to 1,300 and 15,400, respectively, and liver-related mortality to 670 deaths. Using high efficacy treatment alone resulted in 2030 projection of 80,700 viremic cases, 350 HCC cases, 480 liver-related deaths, and 850 and 11,500 decompensated and compensated cirrhosis cases, respectively. With an aggressive treatment strategy, in 2030 there will be about 1,700 viremic cases, 1 HCC case, about 20 liver-related deaths, and 5 and 130 cases of decompensated and compensated cirrhosis, respectively. Delaying this strategy by one year would result in 360 additional deaths by 2030. CONCLUSIONS: HCV in KSA remains constant, and cases of advanced liver disease and mortality continue to rise. Considered increases in treatment efficacy and number treated would have a significantly greater impact than increased treatment efficacy alone. The projected impact will facilitate disease forecasting, resource planning, and strategies for HCV management. Increased screening and diagnosis would likely be required as part of a national strategy.

Amiodarone hepatotoxicity.

Potential hepatotoxicity related to amiodarone therapy is often a concern when deciding whether to initiate or continue treatment with this medication. While mostly associated with long-term oral administration of the drug, toxicity has also been reported early during intravenous administration and months after discontinuation of therapy. In the majority of patients, it is discovered incidentally during routine testing of liver biochemistry and rarely do the hepatic effects develop into symptomatic liver injury or failure. Despite the widespread use of amiodarone, prospective clinical studies have been sparse and there has been little consensus among experts in the field regarding optimum monitoring for adverse effects in patients receiving this drug. In order to examine the current state of knowledge surrounding the incidence, pathogenesis and mechanism of liver effects associated with amiodarone, the existing literature was reviewed, with particular emphasis on clinical recommendations for monitoring.

NOTES: evolving trends in endoscopic surgery.

Intraluminal endoscopic surgery is a recent innovation to minimally invasive surgery. This technique provides access to the peritoneal cavity through a natural orifice. The technique holds the promise for "incisionless," less invasive procedures without the risk of postoperative sequelae as in the standard surgical approach, particularly in high risk patients. The hope of combining the skill and experience of endoscopists and surgeons into a defined specialty has attracted worldwide attention. It is anticipated that the skill sets required will be a hybrid that includes laparoscopic skills as well as endoscopic expertise. The studies in animal models of natural orifice translumenal endoscopic surgery (NOTES) have demonstrated the safety and feasibility of various types of intraabdominal surgeries, including transgastric liver biopsy, cholecystectomy, tubal ligation and peritoneoscopy amongst others. This review discusses the evolution of NOTES, the types of procedures performed and the challenges that lie ahead in the further development of this technique.

Pegylated-interferon alpha 2b and ribavirin for recurrent hepatitis C after liver transplantation: From a Canadian experience to recommendations for therapy.

BACKGROUND: Recurrent hepatitis C (HCV) after liver transplantation (LT) is often more aggressive and treatments tend to be less successful. Pegylated-interferon and ribavirin are the standard of care for the treatment of HCV; however, there is limited published experience of its use after LT. OBJECTIVE: To report the results of pegylated-interferon alpha 2b (PEG-IFN) plus ribavirin for the treatment of recurrent HCV after LT and compare the results with published data. METHODS: Thirteen patients with recurrent HCV were treated with PEG-IFN plus ribavirin. Liver biopsies demonstrated early-stage disease in eight patients and advanced fibrosis in five patients. The average starting dose of PEG-IFN was 0.91 microg/kg (range 0.5 microg/kg to 1.1 microg/kg) per week and ribavirin was started at 662 mg (range 0 mg to 1200 mg) per day. PEG-IFN treatment began an average of 24 months after LT (range six to 73 months). The dose of PEG-IFN was increased in four patients but only two reached 1.5 microg/kg. The ribavirin dose was increased in four, reduced in six and only seven patients reached a ribavirin dose greater than 10.6 mg/kg. RESULTS: A sustained virological response was seen in four of 13 (30.7%) patients and in four of eight (50%) patients with early-stage disease compared with zero of five patients with advanced fibrosis (P=0.1). Cytopenias were common and therapy was poorly tolerated in four of five patients with advanced fibrosis, including acute cellular rejection in three, renal failure in two, liver decompensation in four and death in three. CONCLUSIONS: Although a reasonable sustained virological response can be achieved with the use of PEG-IFN and ribavirin, the treatment is very poorly tolerated by patients with advanced-stage recurrent HCV. Treatment should be instituted before the development of significant fibrosis after LT.